J Cancer 2020; 11(10):3061-3071. doi:10.7150/jca.40191

Research Paper

TNFAIP8 promotes the migration of clear cell renal cell carcinoma by regulating the EMT

Mengya Zhong1,2*, Maoshu Zhu1,3*, Yu Liu2,4, Ying Lin1,3, Lianghai Wang5, Yuhan Ye6, Huiyu Chen1,2, Yan Yang1,2, Guohong Zhuang2,7✉, Jiyi Huang1,3✉

1. Xiang'an Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
2. Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China.
3. The Fifth Hospital of Xiamen, Xiamen, Fujian, China.
4. Department of Gastrointestinal Surgery, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China.
5. Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang, China
6. Department of Pathology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China.
7. Organ Transplantation Institute of Xiamen University, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, Fujian, China.
*These authors contributed equally to this work.

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Citation:
Zhong M, Zhu M, Liu Y, Lin Y, Wang L, Ye Y, Chen H, Yang Y, Zhuang G, Huang J. TNFAIP8 promotes the migration of clear cell renal cell carcinoma by regulating the EMT. J Cancer 2020; 11(10):3061-3071. doi:10.7150/jca.40191. Available from http://www.jcancer.org/v11p3061.htm

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Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastatic potential, and the epithelial-mesenchymal transition (EMT) has been shown to play a key role in multiple cancer progression, migration and metastasis and is the leading cause of poor prognosis. Currently, tumor necrosis factor-α-induced protein 8 (TNFAIP8/TIPE) is a newly discovered tumorigenesis factor, and TNFAIP8 and the EMT influence the migration of renal cancer cells.

Methods: In this study, we first analyzed the relationship between TNFAIP8 and ccRCC using bioinformatics, followed by immunohistochemistry to evaluate the relationship between the two in clinical samples. Subsequently, reverse transcription PCR and western blotting confirmed the expression of TNFAIP8 in ccRCC cells. Furthermore, we measured the migration and invasion abilities by using wound healing and transwell assays after overexpression or knockdown of TNFAIP8 in cells. In addition, we verified whether TNFAIP8 affects the EMT process in ccRCC by quantitative real-time PCR, western blotting, immunohistochemistry and immunofluorescence experiments.

Results: Through database analysis, we found that TNFAIP8 was highly expressed in ccRCC patients and was positively correlated with tumor stage and grade, indicating that TNFAIP8 is associated with the development of advanced ccRCC and poor prognosis. We subsequently confirmed that TNFAIP8 was abnormally overexpressed in clinical samples and ccRCC cell lines and that TNFAIP8 promoted ccRCC cell migration and invasion in vitro. Finally, we found that TNFAIP8 regulated EMT-related molecule expression and regulated the EMT process.

Conclusion: High expression of TNFAIP8 reinforces migration and regulates the EMT in ccRCC, conferring the metastatic potential of ccRCC and suggesting that TNFAIP8 may be a potential therapeutic target for the treatment of advanced ccRCC.

Keywords: TNFAIP8, EMT, ccRCC, migration, metastasis